Children with juvenile arthritis at increased risk for cancer, but UAB research casts doubt on one suspected cause

Children with juvenile idiopathic arthritis are at an increased risk for cancer, but a drug suspected of contributing to that risk may not be the culprit.

Children with juvenile idiopathic arthritis, the most common form of childhood arthritis, appear at least twice as likely to develop cancer compared to children without JIA, irrespective of arthritis medications, according to new research from the University of Alabama at Birmingham published this week in the journal Arthritis and Rheumatism. This report questions the role played by anti-TNF therapy, long considered a potential risk for cancer.

Tumor necrosis factor, or TNF, is thought to contribute to the inflammation common in joint diseases such as arthritis. Anti-TNF therapy, a so-called biologic therapy, is a class of drugs that have been used since 1998. These drugs lessen inflammation by interfering with biologic substances that cause or worsen the inflammatory process.

“Since the introduction of TNF inhibitors in clinical practice, there has been concern about an increased risk of malignancy associated with them,” said Timothy Beukelman, M.D., M.S.C.E., associate professor of pediatric rheumatology and lead investigator of the study.

Beukelman says these concerns prompted the Food and Drug Administration to issue a warning about the possible association between TNF inhibitors and cancer risk in children in 2009.

“The FDA decision was based on data comparing cancer rates in children who received TNF inhibitors compared to children in the general population,” said Beukelman. “Those analyses did not account for exposure to arthritis drugs other than TNF inhibitors, such as methotrexate, or for possible carcinogenic effects of the JIA disease process itself.”

Beukelman’s team studied national Medicaid administrative claims billing data from all 50 U.S. states collected from 2000 through 2005 to identify 7,812 children diagnosed with JIA. Among these children, 1,484 received treatment with anti-TNF drugs.

The team compared the children with JIA to a control group of children without JIA, but with a different chronic illness such as asthma or ADHD. The cancer rate for the non-JIA group was 13 to 17 per 100,000 person years (number of patients multiplied by the number of years of observation). The children with JIA had a cancer rate of 55 per 100,000 person-years, an increase of three to four times.

Interestingly, the research team identified no malignancies in participants with JIA who had been treated with anti-TNF therapy, though the number of children studied was relatively small.

“It appears clear that there is an increased risk of malignancy in children with JIA, but it’s not all attributable to TNF inhibitors,” said Beukelman. “At least part of the increased risk, and perhaps even all of it, appears to be attributable to the disease itself, or to other medications used in treatment such as methotrexate.”

Beukelman said that how disease activity and uncontrolled inflammation in JIA influences the risk of cancer is not known, pointing out that the study team did not have access to that kind of clinical information in this type of administrative database.

“TNF inhibitors may possibly be associated with an increased risk of cancer; our study did not have enough patients to definitively answer this question,” he said. “But based on our findings, the amount of risk that the TNF inhibitors may be responsible for appears to be much smaller than initially suspected.”

As many as one child in every 1,000 develops JIA, and JIA can affect children at any age. It is estimated that around 300,000 children in the U.S. have been diagnosed with JIA. There are several types of JIA, all involving chronic joint inflammation. This inflammation begins before patients reach the age of 16, may involve one or many joints, and can cause other symptoms such as fevers, rash and/or eye inflammation and even cause inflammation of the internal organs. Chronic arthritis often continues into adulthood and may lead to significant pain and life-long disability.